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Review

Efficacy of immune checkpoint inhibitors in different types of melanoma

ORCID Icon, , , , , , , , , , , , , ORCID Icon, & show all
Pages 4-13 | Received 25 Feb 2020, Accepted 14 May 2020, Published online: 14 Jul 2020

References

  • Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, Gavin A, Visser O, Gavin A, Bray F. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356–387. doi:10.1016/j.ejca.2018.07.005.
  • Chang AE, Karnell LH, Menck HR. The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1998; 83:1664–1678. doi:10.1002/(sici)1097-0142(19981015)83:8<1664:: aid-cncr23>3.0.co;2-g.
  • McLaughlin CC, Wu XC, Jemal A, Martin HJ, Roche LM, Chen VW. Incidence of noncutaneous melanomas in the US. Cancer. 2005;103:1000–1007. doi:10.1002/cncr.20866.
  • HicKs, MJ, Flaitz CM. Oral mucosal melanoma: epidemiology and pathobiology. Oral Oncol. 2000;36:152–169.
  • Singh AD, Topham A. Incidence of uveal melanoma in the United States: 1973-1997. Ophthalmol. 2003;110(5):956–61. 10.1016/S0161-6420(03)00078-2.
  • Hu DN, Yu G, McCormick SA, Finger PT. Population-based incidence of conjunctival melanoma in various races and ethnic groups and comparison with other melanomas. Am J Ophthalmol. 2008;145:418–423. doi:10.1016/j.ajo.2007.10.022.
  • Furney SJ, Turajlic S, Stamp G, Thomas JM, Hayes A, Strauss D, Gavrielides M, Xing W, Gore M, Larkin J, Marais R. The mutational burden of acral melanoma revealed by whole-genome sequencing and comparative analysis. Pigment Cell Melanoma Res. 2014;27(5):835–8. doi: 10.1111/pcmr.12279.
  • Buqué A, Bloy N, Aranda F, Castoldi F, Eggermont A, Cremer I, Fridman WH, Fucikova J, Galon J, Marabelle A, et al. Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications. Oncoimmunol. 2015;4(4):e1008814. doi:10.1080/2162402X.2015.1008814.
  • Tarhini A, Lo E, Minor DR. Releasing the brake on the immune system: ipilimumab in melanoma and other tumors. Cancer Biother Radiopharm. 2010; 25(6):601–613. doi:10.1089/cbr.2010.0865.
  • Shrikant P, Khoruts A, Mescher MF. CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism. Immunity. 1999;11(4):483–493. doi:10.1016/s1074-7613(00)80123-5.
  • Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363(8):711–723. doi:10.1056/NEJMoa1003466.
  • McDermott D, Haanen J, Chen TT, Lorigan P, O'Day S, for the MDX010-20 investigators. Efficacy and safety of ipilimumab in metastatic melanoma patients surviving more than 2 years following treatment in a phase III trial (MDX010-20). Ann Oncol. 2013; 24(10):2694–2698. doi:10.1093/annonc/mdt291.
  • Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, et al. ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011;364(26):2517–2526. doi:10.1056/NEJMoa1104621.
  • Maio M, Grob JJ, Aamdal S, Bondarenko I, Robert C, Thomas L, Garbe C, Chiarion-Sileni V, Testori A, Chen TT, Tschaika M, Wolchok JD. Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial. J Clin Oncol. 2015;33(10):1191–1196. doi:10.1200/JCO.2014.56.6018.
  • Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol. 2015;33(17):1889–1894. doi:10.1200/JCO.2014.56.2736.
  • Ascierto PA, Del Vecchio M, Robert C, Mackiewicz A, Chiarion-Sileni V, Arance A, Lebbé C, Bastholt L, Hamid O, Rutkowski P, et al. ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2017;18(5):611–622. doi:10.1016/S1470-2045(17)30231-0.
  • Margolin K, Ernstoff MS, Hamid O, Lawrence D, McDermott D, Puzanov I, Wolchok JD, Clark JI, Sznol M, Logan TF, et al. ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol. 2012;13(5):459–465. doi:10.1016/S1470-2045(12)70090-6.
  • Di Giacomo AM, Ascierto PA, Queirolo P, Pilla L, Ridolfi R, Santinami M, Testori A, Simeone E, Guidoboni M, Maurichi A, et al. Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian Network for Tumor Biotherapy (NIBIT)-M1 phase II study. Ann Oncol. 2015;26(4):798–803. doi:10.1093/annonc/mdu577.
  • Johnson DB, Peng C, Abramson RG, Ye F, Zhao S, Wolchok JD, Sosman JA, Carvajal RD, Ariyan C. Clinical activity of ipilimumab in acral melanoma: a retrospective review. Oncologist 2015;20(6):648–52. doi: 10.1634/theoncologist.2014-0468.
  • Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev. 2010;236:219–242. doi:10.1111/j.1600-065X.2010.00923.x.
  • Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–330. doi:10.1056/NEJMoa1412082.
  • Ascierto PA, Long GV, Robert C, Brady B, Dutriaux C, Di Giacomo AM, Mortier L, Hassel JC, Rutkowski P, McNeil C, et al. Survival outcomes in patients with previously untreated braf wild-type advanced melanoma treated with nivolumab therapy: three-year follow-up of a randomized phase 3 trial. JAMA Oncol. 2019;5(2):187–194. doi:10.1001/jamaoncol.2018.4514.
  • Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH Jr, Lao CD, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16(4):375–84. doi:10.1016/S1470-2045(15)70076-8.
  • Larkin J, Minor D, D'Angelo S, Neyns B, Smylie M, Miller WH Jr, Gutzmer R, Linette G, Chmielowski B, Lao CD, et al. Overall survival in patients with advanced melanoma who received nivolumab versus investigator's choice chemotherapy in CheckMate 037: a randomized, controlled, open-label phase III trial. J Clin Oncol. 2018;36(4):383–390. doi:10.1200/JCO.2016.71.8023.
  • Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–2532. doi:10.1056/NEJMoa1503093.
  • Robert C, Long GV, Schachter J, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil CM, Lotem M, et al. Long-term outcomes in patients (pts) with ipilimumab (ipi)-naive advanced melanoma in the phase 3 KEYNOTE-006 study who completed pembrolizumab (pembro) treatments. J Clin Oncol. 2017; 35,15_suppl:9504-9504. doi:10.1200/JCO.2017.35.15_suppl.9504.
  • Long GV, Schachter J, Ribas A, Arance AM, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil CM, Lotem M, et al. 4-year survival and outcomes after cessation of pembrolizumab (pembro) after 2-years in patients (pts) with ipilimumab (ipi)-naive advanced melanoma in KEYNOTE-006. J Clin Oncol 2018; 36,15_suppl,9503-9503. doi:10.1200/JCO.2018.36.15_suppl.9503.
  • Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017;390(10105):1853–1862. doi:10.1016/S0140-6736(17)31601-X.
  • Robert C, Ribas A, Schachter J, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil CM, Lotem M, et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol. 2019;20(9):1239–1251. doi:10.1016/S1470-2045(19)30388-2.
  • Petrella TM, Robert C, Richtig E, Miller WH Jr, Masucci GV, Walpole E, Lebbe C, Steven N, Middleton MR, Hille D, et al. Patient-reported outcomes in KEYNOTE-006, a randomised study of pembrolizumab versus ipilimumab in patients with advanced melanoma. Eur J Cancer. 2017;86:115–124. doi:10.1016/j.ejca.2017.08.032.
  • Carlino MS, Long GV, Schadendorf D, Robert C, Ribas A, Richtig E, Nyakas M, Caglevic C, Tarhini A, Blank C, et al. Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A randomised clinical trial. Eur J Cancer. 2018;101:236–243. doi:10.1016/j.ejca.2018.06.034.
  • Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, Tsiouris AJ, Cohen J, Vortmeyer A, Jilaveanu L, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol. 2016;17(7):976–983. doi:10.1016/S1470-2045(16)30053-5.
  • Iga N, Otsuka A, Hirata M, Kataoka TR, Irie H, Nakashima C, Matsushita S, Uchi H, Yamamoto Y, Funakoshi T, et al. Variable indoleamine 2,3-dioxygenase expression in acral/mucosal melanoma and its possible link to immunotherapy. Cancer Sci. 2019;110(11):3434–3441. doi: 10.1111/cas.14195.
  • Shoushtari AN, Munhoz RR, Kuk D, Ott PA, Johnson DB, Tsai KK, Rapisuwon S, Eroglu Z, Sullivan RJ, Luke JJ, et al. The efficacy of anti-PD-1 agents in acral and mucosal melanoma. Cancer. 2016;122(21):3354–3362. doi: 10.1002/cncr.30259.
  • Nathan P, Ascierto PA, Haanen J, Espinosa E, Demidov L, Garbe C, Guida M, Lorigan P, Chiarion-Sileni V, Gogas H, et al. Safety and efficacy of nivolumab in patients with rare melanoma subtypes who progressed on or after ipilimumab treatment: a single-arm, open-label, phase II study (CheckMate 172). Eur J Cancer. 2019;119:168–178. doi: 10.1016/j.ejca.2019.07.010.
  • Nakamura Y, Namikawa K, YoshinonK, Yoshikawa S, Uchi H, Goto K, Nakamura Y, Fukushima S, Kiniwa nY, Takenouchi T, et al. Real-world efficacy of anti-PD-1 antibodies in advanced acral melanoma patients: a retrospective, multicenter study (JAMP study). ASCO 2019 abstract 9529
  • Keilholz U, Mehnert JM, Bauer S, Bourgeois H, Patel MR, Gravenor D, Nemunaitis JJ, Taylor MH, Wyrwicz L, Lee KW, Kasturi V, Chin K, von Heydebreck A, Gulley JL. Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2019 7(1):12. doi: 10.1186/s40425-018-0459-y.
  • Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012 366(26):2455–65. doi: 10.1056/NEJMoa1200694.
  • Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A 2010;107:4275–4280. doi: 10.1073/pnas.0915174107.
  • Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372(21):2006–2017. doi:10.1056/NEJMoa1414428.
  • Hodi FS, Chesney J, Paclik AC, Robert C, Grossmann KF, McDermott DF, Linette GP, Meyer N, Giguere JK, Agarwala SS, et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016;17(11):1558–1568. doi: 10.1016/S1470-2045(16)30366-7.
  • Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23–34. doi:10.1056/NEJMoa1504030.
  • Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Wagstaff J, Schadendorf D, Ferrucci PF, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377(14):1345–1356. doi:10.1056/NEJMoa1709684.
  • Larkin JMG, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao C, Cowey CL, Schadendorf D, Wagstaff J, Dummer R, et al. Five-year survival with combined nivolumab and Ipilimumb in advanced melanoma. N Engl J Med. 2019;381(16):1535–1546. doi: 10.1056/NEJMoa1910836.
  • Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, Wilmott JS, Edwards J, Gonzalez M, Scolyer RA, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018;19(5):672–681. doi:10.1016/S1470-2045(18)30139-6.
  • Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, Khushalani NI, Lewis K1, Lao CD, Postow MA, et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018; 379(8):722–730. doi:10.1056/NEJMoa1805453.
  • Namikawa K, Kiyohara Y, Takenouchi T, Uhara H, Uchi H, Yoshikawa S, Takatsuka S, Koga H, Wada N, Minami H, et al. Efficacy and safety of nivolumab in combination with ipilimumab in Japanese patients with advanced melanoma: An open-label, single-arm, multicentre phase II study. Eur J Cancer. 2018;105:114–126. doi: 10.1016/j.ejca.2018.09.025.
  • Eggermont AM, Charion-Sileni V, Grobb JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16(5):522–30. doi:10.1016/S1470-2045(15)70122-1.
  • Coens C, Suciu S, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, et al. Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial. Lancet Oncol. 2017;18(3):393–403. doi:10.1016/S1470-2045(17)30015-3.
  • Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375(19):1845–1855. doi:10.1056/NEJMoa1611299.
  • Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, Dalle S, Schenker M, Chiarion-Sileni V, Marquez-Rodas I, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824–1835. doi:10.1056/NEJMoa1709030.
  • Weber J, Del Vecchio M, Mandalà M, Gogas H, Arance AM, Dalle S, Cowey CL, Schenker M, Grob JJ, Chiarion-Sileni V, et al. Adjuvant nivolumab (NIVO) versus ipilimumab (IPI) in resected stage III/IV melanoma: 3-year efficacy and biomarker results from the phase 3 CheckMate 238 trial. Ann Oncol. 2019;30( suppl_5):v533–v563. doi:10.1093/annonc/mdz255.
  • Eggermont A, Blank C, Mandala M, Long GV, Atkinson V, Dalle S, Haydon A, Lichinitser M, Khattak A, Carlino MS, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018; 378(19):1789–1801. doi:10.1056/NEJMoa1802357.
  • Pelster MS, Amaria RN. Combined targeted therapy and immunotherapy in melanoma: a review of the impact on the tumor microenvironment and outcomes of early clinical trials. Ther Adv Med Oncol. 2019;11:1758835919830826. doi:10.1177/1758835919830826.
  • Boni A, Cogdill AP, Dang P, Udayakumar D, Njauw CN, Sloss CM, Ferrone CR, Flaherty KT, Lawrence DP, Fisher DE, et al. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res. 2010;70(13):5213–5219. doi:10.1158/0008-5472.CAN-10-0118.
  • Simeone E, Grimaldi AM, Festino L, Giannarelli D, Vanella V, Palla M, Curvietto M, Esposito A, Palmieri G, Mozzillo N, Ascierto PA. Correlation between previous treatment with BRAF inhibitors and clinical response to pembrolizumab in patients with advanced melanoma. Oncoimmunology. 2017;6(3):e1283462. doi:10.1080/2162402X.2017.1283462.
  • Ackerman A, Klein O, McDermott DF, Wang W, Ibrahim N, Lawrence DP, Gunturi A, Flaherty KT, Hodi FS, Kefford R, et al. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer. 2014;120(11):1695–1701. doi:10.1002/cncr.28620.
  • Ribas A, Lawrence D, Atkinson V, Agarwal S, Miller WH Jr, Carlino MS, Fisher R, Long GV, Hodi FS, Tsoi J, et al. Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma. Nat Med. 2019;25(6):936–940. doi:10.1038/s41591-019-0476-5.
  • Ascierto PA, Ferrucci PF, Fisher R, Del Vecchio M, Atkinson V, Schmidt H, Schachter J, Queirolo P, Long GV, Di Giacomo AM, et al. Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma. Nat Med. 2019;25(6):941–946. doi:10.1038/s41591-019-0448-9.
  • Sullivan RJ, Hamid O, Gonzalez R, Infante JR, Patel MR, Hodi FS, Lewis KD, Tawbi HA, Hernandez G, Wongchenko MJ, et al. Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients. Nat Med. 2019;25(6):929–935. doi: 10.1038/s41591-019-0474-7.
  • Miller WH, Min Kim T, Lee CB, Flaherty KT, Reddy S, Jamal R, Chow LQ, Rooney IA, Pitcher B, Cha E, Infante JR. Atezolizumab (A) + cobimetinib (C) in metastatic melanoma (mel): Updated safety and clinical activity. J Clin Oncol. 2017;35, 15_suppl,3057-3057. doi:10.1200/JCO.2017.35.15_suppl.3057.
  • Long GV, Lebbe C, Atkinson V, Mandalà M, Nathan PD, Arance Fernandez AM, Richtig E, Yamazaki N, Robert C, Schadendorf D, et al. The anti–PD-1 antibody spartalizumab (S) in combination with dabrafenib (D) and trametinib (T) in previously untreated patients (pts) with advanced BRAF V600–mutant melanoma: Updated efficacy and safety from parts 1 and 2 of COMBI-i. J Clin Oncol. 2019;37,15_suppl, 9531–9531. doi:10.1200/JCO.2019.37.15_suppl.9531.
  • Postow MA, Hamid O, Carvajal RD. Mucosal melanoma: pathogenesis, clinical behavior, and management. Curr Oncol Rep. 2012;14(5):441–448. doi:10.1007/s11912-012-0244-x.
  • Rossi E, Schinzari G, Maiorano BA, Pagliara MM, Di Stefani A, Bria E, Peris K, Blasi MA, Tortora G. Conjunctival melanoma: genetic and epigenetic insights of a distinct type of melanoma. Int J Mol Sci. 2019;20(21). doi: 10.3390/ijms20215447.
  • Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Bröcker EB, LeBoit PE, Pinkel D, Bastian BC. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135–2147. doi:10.1056/NEJMoa050092.
  • Beadling C, Jacobson-Dunlop E, Hodi FS, Le C, Warrick A, Patterson J, Town A, Harlow A, Cruz F 3rd, Azar S, et al. KIT gene mutations and copy number in melanoma subtypes. Clin Cancer Res. 2008; 14(21):6821–6828. doi:10.1158/1078-0432.CCR-08-0575.
  • Newell F, Kong Y, Wilmott JS, Johansson PA, Ferguson PM, Cui C, Li Z, Kazakoff SH, Burke H, Dodds TJ, et al. Whole-genome landscape of mucosal melanoma reveals diverse drivers and therapeutic targets. Nat Commun. 2019;10(1):3163. doi: 10.1038/s41467-019-11107-x.
  • D'Angelo SP, Larkin J, Sosman JA, Lebbé C, Brady B, Neyns B, Schmidt H, Hassel JC, Hodi FS, Lorigan P, et al. Efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with mucosal melanoma: a pooled analysis. J Clin Oncol. 2017;35:226–235. doi:10.1200/JCO.2016.67.9258.
  • Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32(10):1020–1030. doi:10.1200/JCO.2013.53.010.
  • Urba WJ, Martin-Algarra S, Callahan M, Wolchok JD, Sharfman WH, Sosman JA, Bhatia S, Hwu WJ, Gajewski TF, Slingluff CL, et al. Immunomodulatory activity of nivolumab monotherapy in patients with advanced melanoma. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015; 75(15Suppl): Abstract nr 2855. doi:10.1158/1538-7445.AM2015-2855.
  • Hamid O, Robert C, Ribas A, Hodi FS, Walpole E, Daud A, Arance AS, Brown E, Hoeller C, Mortier L, et al. Antitumour activity of pembrolizumab in advanced mucosal melanoma: a post-hoc analysis of KEYNOTE-001, 002, 006. Br J Cancer. 2018;119(6):670–674. doi:10.1038/s41416-018-0207-6.
  • Ribas A, Hamid O, Daud A, Hodi FS, Wolchok JD, Kefford R, Joshua AM, Patnaik A, Hwu WJ, Weber JS, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA. 2016;315(15):1600–1609. doi: 10.1001/jama.2016.4059.
  • Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, Hodi FS, Schachter J, Pavlick AC, Lewis KD, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908–918. doi:10.1016/S1470-2045(15)00083-2.
  • Singh AD, Borden EC. Metastatic uveal melanoma. Ophthalmol Clin North Am 2005; 18:143–150. doi:10.1016/j.ohc.2004.07.003.
  • Schinzari G, Rossi E, Cassano A, Dadduzio V, Quirino M, Pagliara M, Blasi MA, Barone C. Cisplatin, dacarbazine and vinblastine as first line chemotherapy for liver metastatic uveal melanoma in the era of immunotherapy: a single institution phase II study. Melanoma Res. 2017 Dec;27(6):591–595. doi: 10.1097/CMR.0000000000000401.
  • Karydis I, Chan PY, Wheater M, Arriola E, Szlosarek PW, Ottensmeier CH. Clinical activity and safety of pembrolizumab in ipilimumab pre-treated patients with uveal melanoma. Oncoimmunol. 2016;5(5):e1143997. doi:10.1080/2162402X.2016.1143997.
  • Algazi AP, Tsai KK, Shoushtari AN, Munhoz RR, Eroglu Z, Piulats JM, Ott PA, Johnson DB, Hwang J, Daud AI, et al. Clinical outcomes in metastatic uveal melanoma treated with PD-1 and PD-L1 antibodies. Cancer. 2016;122(21):3344–3353. doi:10.1002/cncr.30258.
  • Rossi E, Pagliara MM, Orteschi D, Dosa T, Sammarco MG, Caputo CG, Petrone G, Rindi G, Zollino M, Blasi MA, Cassano A, Bria E, Tortora G, Schinzari G. Pembrolizumab as first-line treatment for metastatic uveal melanoma. Cancer Immunol Immunother. 2019;68(7):1179–1185. doi:10.1007/s00262-019-02352-6.
  • Heppt MV, Amaral T, Kähler KC, Heinzerling L, Hassel JC, Meissner M, Kreuzberg N, Loquai C, Reinhardt L, Utikal J, Dabrowski E, Gesierich A, Pföhler C, Terheyden P, Thoms KM, Zimmer L, Eigentler TK, Kirchberger MC, Stege HM, Meier F, Schlaak M, Berking C. Combined immune checkpoint blockade for metastatic uveal melanoma: a retrospective, multi-center study. J Immunother Cancer. 2019;7(1):299–207. doi: 10.1186/s40425-019-0800-0
  • Rossi E, Schinzari G, Zizzari IG, Maiorano BA, Pagliara MM, Sammarco MG, Fiorentino V, Petrone G, Cassano A, Rindi G, Bria E, Blasi MA, Nuti M, Tortora G. Immunological Backbone of Uveal Melanoma: Is There a Rationale for Immunotherapy? Cancers (Basel). 2019; 11(8).pii: E1055. doi: 10.3390/cancers11081055.
  • Johnson CP, Kim IK, Esmaeli B, Amin-Mansour A, Treacy DJ, Carter SL, Hodis E, Wagle N, Seepo S, Yu X, et al. Systematic genomic and translational efficiency studies of uveal melanoma. PLoS One. 2017 Jun 8;12(6):e0178189. doi: 10.1371/journal.pone.0178189.
  • Rossi E, Maiorano BA, Pagliara MM, Sammarco MG, Dosa T, Martini M, Rindi G, Bria E, Blasi MA, Tortora G, Schinzari G. Dabrafenib and trametinib in BRAF Mutant Metastatic Conjunctival Melanoma. Front Oncol. 2019;9:232. doi:10.3389/fonc.2019.00232
  • Kini A, Fu R, Compton C, Miller DM, Ramasubramanian A. Pembrolizumab for recurrent conjunctival melanoma. JAMA Ophthalmol. 2017;135(8),891. doi:10.1001/jamaophthalmol.2017.2279.
  • Pinto Torres S, André T, Gouveia E, Costa L, Passos MJ. Systemic treatment of metastatic conjunctival melanoma. Case Rep Oncol Med. 2017;2017:4623964. doi:10.1155/2017/4623964.
  • Ford J, Thuro BA, Thakar S, Hwu W, Richani K, Esmaeli B. Immune checkpoint inhibitors for treatment of metastatic melanoma of the orbit and ocular adnexa. Ophthal Plast Reconstr Surg. 2017;20,20. doi:10.1097/IOP.0000000000000790.
  • Finger PT, Pavlick AC. Checkpoint inhibition immunotherapy for advanced local and systemic conjunctival melanoma: a clinical case series. J Immunother Cancer. 2019;7(1):83. doi: 10.1186/s40425-019-0555-7.
  • Sagiv O, Thakar SD, Kandl TJ, Ford J, Sniegowski MC, Hwu WJ, Esmaeli B: Immunotherapy with Programmed cell Death 1 inhibitors for 5 patients with conjunctival melanoma. JAMA Ophthalmol. 2018;136(11):1236–1241. doi:10.1001/jamaophthalmol.2018.3488.
  • Chaves LJ, Huth B, Augsburger JJ, Correa ZM. Eye-Sparing Treatment for Diffuse Invasive Conjunctival Melanoma. Ocul Oncol Pathol. 2018;4(4):261–266. doi: 10.1159/000485978.
  • Cao J, Brouwer NJ, Richards KE, Marinkovic M, van Duinen S, Hurkmans D, Verdegaal EME, Jordanova ES, Jager MJ. PD-L1/PD-1 expression and tumor-infiltrating lymphocytes in conjunctival melanoma. Oncotarget. 2017;8(33):54722–54734. doi:10.18632/oncotarget.18039.
  • Swaminathan SS, Field MG, Sant D, Wang G, Galor A, Dubovy SR, Harbour JW, Karp CL. Molecular Characteristics of Conjunctival Melanoma Using Whole-Exome Sequencing. JAMA Ophthalmol. 2017;135(12):1434–1437. doi: 10.1001/jamaophthalmol.2017.4837.